{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:38:17Z","timestamp":1793385497031,"version":"4.5.0"},"reference-count":184,"publisher":"American Chemical Society (ACS)","issue":"27","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Indian Council of Medical Research (ICMR), New Delhi, Goverment of India","award":["3\/2\/2\/16\/2022-NCD-III"],"award-info":[{"award-number":["3\/2\/2\/16\/2022-NCD-III"]}]},{"name":"Indian Council of Medical Research (ICMR), New Delhi, Goverment of India","award":["OMI\/10\/2022\/ECD"],"award-info":[{"award-number":["OMI\/10\/2022\/ECD"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Helicobacter pylori, a Gram-negative bacterium, exhibits unique adaptations to thrive in an acidic gastric environment. Urease enzyme present in the bacteria converts urea to ammonia and carbon dioxide, making the surrounding acidic environment of the bacteria neutral. This adaptation helps the bacteria to survive and travel further to gastric epithelial cells, where it attaches to mucin and damages the tissues, leading to gastritis, peptic ulcer, and ultimately, cancer. Physicians typically prescribe first-, second-, and third-line antibiotic therapies to eliminate the bacterium, but these treatments frequently fail to achieve complete eradication. This failure, driven by factors such as the coccoid form, high bacterial load, and biofilm formation, contributes to the growing problem of antibiotic resistance. Targeting urease activity presents a promising strategy to reduce the H. pylori pathogenicity and enhance its susceptibility to antibiotics. Inhibiting urease enzyme activity would be an option to make the bacteria less pathogenic and more prone to antibiotic treatment. Including the urease inhibitors as an adjuvant with the current antibiotic treatment regimen would effectively eradicate the bacteria. This comprehensive review discusses the structural characteristics of the urease enzyme and its role in pathogenesis and the available urease inhibitors along with their pharmacophoric features. An elaborative pharmacophore-based screening and docking study on scaffolds such as chlorogenic acid, catechol, and hydroxamic acid to discover a potent urease inhibitor is a future scope identified in this review.<\/jats:p>","DOI":"10.1021\/acsomega.5c02725","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T13:55:29Z","timestamp":1751637329000},"page":"28643-28669","source":"Crossref","is-referenced-by-count":22,"title":["Targeting Urease:\nA Promising Adjuvant Strategy for\nEffective\n                    <i>Helicobacter pylori<\/i>\n                    Eradication"],"prefix":"10.1021","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8972-2148","authenticated-orcid":true,"given":"Shivani","family":"Kunkalienkar","sequence":"first","affiliation":[{"name":"Manipal Academy of Higher Education , , , ,","place":["Manipal, Karnataka, India, 576 104"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3119-6731","authenticated-orcid":true,"given":"Neha S.","family":"Gandhi","sequence":"additional","affiliation":[{"name":"Manipal Academy of Higher Education , , ,","place":["Manipal, India, 576 104"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashutosh","family":"Gupta","sequence":"additional","affiliation":[{"name":"Manipal Academy of Higher Education , , , ,","place":["Manipal, Karnataka, India, 576 104"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moumita","family":"Saha","sequence":"additional","affiliation":[{"name":"Manipal Academy of Higher Education , , , ,","place":["Manipal, Karnataka, India, 576 104"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aravinda","family":"Pai","sequence":"additional","affiliation":[{"name":"Manipal Academy of Higher Education , , , ,","place":["Manipal, Karnataka, India, 576 104"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiran","family":"Shetty","sequence":"additional","affiliation":[{"name":"Manipal Academy of Higher Education , , , ,","place":["Manipal, Karnataka, India, 576 104"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7901-1818","authenticated-orcid":true,"given":"Abhishek","family":"Gupta","sequence":"additional","affiliation":[{"name":"University of Wolverhampton , , Wulfruna Street , ,","place":["Wolverhampton, U.K., WV1 1LY"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namdev","family":"Dhas","sequence":"additional","affiliation":[{"name":"Manipal Academy of Higher Education , , , ,","place":["Manipal, Karnataka, India, 576 104"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghu Chandrashekar","family":"Hariharapura","sequence":"additional","affiliation":[{"name":"Manipal Academy of Higher Education , , , ,","place":["Manipal, Karnataka, India, 576 104"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6653-4660","authenticated-orcid":true,"given":"K.","family":"Nandakumar","sequence":"additional","affiliation":[{"name":"Manipal Academy of Higher Education , , , ,","place":["Manipal, Karnataka, India, 576 104"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagalakshmi","family":"Narasimhaswamy","sequence":"additional","affiliation":[{"name":"Manipal University College Malaysia , , ,","place":["Melaka, Malaysia, 75150"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5341-0981","authenticated-orcid":true,"given":"Sudheer","family":"Moorkoth","sequence":"additional","affiliation":[{"name":"Manipal Academy of Higher Education , , , ,","place":["Manipal, Karnataka, India, 576 104"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"issue":"1","key":"2026081812134405200_cit1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41572-023-00431-8","article-title":"Helicobacter\npylori infection","volume":"9","author":"Malfertheiner","year":"2023","journal-title":"Nat. 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Cochrane\nDatabase of Systematic Reviews. https:\/\/www.cochranelibrary.com\/cdsr\/doi\/10.1002\/14651858.CD002096.pub2\/abstract, accessed on  February 12, 2025."},{"issue":"10","key":"2026081812134405200_cit7","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1016\/j.cgh.2018.12.014","article-title":"Effects of anti-Helicobacter pylori therapy on incidence of autoimmune diseases, including inflammatory\nbowel diseases","volume":"17","author":"Lin","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"issue":"2","key":"2026081812134405200_cit8","doi-asserted-by":"publisher","first-page":"260","DOI":"10.4293\/108680812X13427982376860","article-title":"The Effect of Helicobacter\npylori on Gastroesophageal Reflux Disease","volume":"16","author":"Polat","year":"2012","journal-title":"J.\nSoc. Laparoendosc. 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Hepatol."},{"issue":"17","key":"2026081812134405200_cit30","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s00535-006-1938-3","article-title":"Guidelines\nfor the management of Helicobacter pylori infection\nin Japan: current status and future prospects","volume":"42","author":"Fujioka","year":"2007","journal-title":"J. Gastroenterol."},{"issue":"6","key":"2026081812134405200_cit31","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.3748\/wjg.v20.i6.1517","article-title":"Second and third line treatment options for Helicobacter pylori eradication","volume":"20","author":"Song","year":"2014","journal-title":"World\nJ. Gastroenterol."},{"issue":"1","key":"2026081812134405200_cit32","doi-asserted-by":"publisher","DOI":"10.1111\/eci.12857","article-title":"Treatment of Helicobacter pylori infection: A clinical practice update","volume":"48","author":"Zagari","year":"2018","journal-title":"Eur. J. Clin. 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J."},{"issue":"S1","key":"2026081812134405200_cit40","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/hel.12251","article-title":"Pathogenesis of Helicobacter pylori\nInfection","volume":"20","author":"Sgouras","year":"2015","journal-title":"Helicobacter"},{"issue":"sup187","key":"2026081812134405200_cit41","doi-asserted-by":"publisher","first-page":"39","DOI":"10.3109\/00365529109098223","article-title":"Helicobacter pylori Urease: Properties\nand Role in Pathogenesis","volume":"26","author":"Mobley","year":"1991","journal-title":"Scand. J. Gastroenterol."},{"issue":"1","key":"2026081812134405200_cit42","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1111\/j.1574-6968.1991.tb04158.x","article-title":"Characterisation\nof the urease from Helicobacter\npylori and comparison with the ureases from related spiral\ngastric bacteria","volume":"76","author":"Turbett","year":"1991","journal-title":"FEMS Microbiol. 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Chem."},{"issue":"1","key":"2026081812134405200_cit48","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1042\/BJ20090434","article-title":"Helicobacter\npylori UreE, a urease accessory protein: specific Ni2+- and Zn2+-binding properties and interaction\nwith its cognate UreG","volume":"422","author":"Bellucci","year":"2009","journal-title":"Biochem. 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